H.C. Diener (Hans Christoph)http://repub.eur.nl/ppl/27724/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryRelation Between Aspirin Dose, All-Cause Mortality, and Bleeding in Patients With Recent Cerebrovascular or Coronary Ischemic Events (from the BRAVO Trial)http://repub.eur.nl/pub/29202/
Sat, 15 Nov 2008 00:00:01 GMT<div>H.D. Aronow</div><div>R.M. Califf</div><div>R.A. Harrington</div><div>M. Vallee</div><div>C. Graffagnino</div><div>A. Shuaib</div><div>D. Fitzgerald</div><div>J.D. Easton</div><div>F.J.J. van de Werf</div><div>H.C. Diener</div><div>J.J. Ferguson</div><div>P.J. Koudstaal</div><div>P. Amarenco</div><div>P. Theroux</div><div>S.M. Davis</div><div>E.J. Topol</div>
Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (<162 mg vs ≥162 mg/day aspirin) and clinical outcome in 4,589 placebo-treated patients enrolled in the Blockage of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO) trial over a median follow-up of 366 days. Standard Cox regression analysis was employed because propensity analysis was not feasible. Compared with lower aspirin doses, higher doses were associated with lower unadjusted all-cause mortality (2.9 vs 1.6%, respectively; log rank chi-square 8.6, p = 0.0034). Higher aspirin dose remained independently predictive of lower all-cause mortality in a multivariable Cox proportional hazards model (hazard ratio 0.64, 95% confidence interval 0.42 to 0.97, p = 0.037). However, there was no significant difference in the incidence of the composite endpoint death, nonfatal myocardial infarction, or nonfatal stroke (6.1% vs 6.2%, p = 0.74). Higher aspirin dose was a significant independent predictor of any (hazard ratio 1.32, 95% confidence interval 1.12 to 1.55, p = 0.001) but not serious bleeding. In conclusion, our findings suggest that aspirin doses of ≥162 mg/day may be more beneficial than those <162 mg/day at preventing death. Erratum: Design and baseline characteristics of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) study (Cerebrovascular Diseases (2003) 16 (389-395))http://repub.eur.nl/pub/52815/
Tue, 10 Feb 2004 00:00:01 GMT<div>D. Crimmins</div><div>S.M. Davis</div><div>S. Dimmitt</div><div>G. Donnan</div><div>J. Frayne</div><div>D. Freilich</div><div>D. Gillies</div><div>J. Mikocki</div><div>C. Schmidauer</div><div>R. Schmidt</div><div>J. de Bleecker</div><div>G. Deceuninck</div><div>P. Tack</div><div>V. Thijs</div><div>W. Robberecht</div><div>J. Gomes Fernandes</div><div>M. Beaudry</div><div>R. Cote</div><div>K. Hoyte</div><div>L.-H. Lebrun</div><div>D.J. Sahlas</div><div>M.D. Norris</div><div>D. Selchen</div><div>A. Shuaib</div><div>J. Simard</div><div>J.D. Spence</div><div>T.H. Teal</div><div>M. Winger</div><div>G. Matamala</div><div>A. Jaramillo</div><div>R. Cifkova</div><div>Z. Kalita</div><div>I. Rektor</div><div>H. Rosolova</div><div>R. Stipal</div><div>D. Vaclavik</div><div>G. Boysen</div><div>H. Iversen</div><div>A.R. Anderson</div><div>H. Sillesen</div><div>M. Hillbom</div><div>M. Kaste</div><div>H. Numminen</div><div>A. Pilke</div><div>A. Salmivaara</div><div>O. Pammo</div><div>J. Sivenius</div><div>P. Amarenco</div><div>J. Boulliat</div><div>T. de Broucker</div><div>P. Chollet</div><div>M.-H. Mahagne</div><div>L. Milandre</div><div>D. de Moulin</div><div>E. Roullet</div><div>U. Bogdahn</div><div>O. Busse</div><div>H.C. Diener</div><div>R. Haberl</div><div>G. Hamann</div><div>L. Harms</div><div>A. Hendrich</div><div>G. Kroczek</div><div>M.G. Hennerici</div><div>W. Knecht</div><div>H. Henningsen</div><div>C. Lichy</div><div>V. Grau</div><div>D. Sander</div><div>D. Schneider</div><div>J. Berrouschot</div><div>C. Karageorgiou</div><div>A. Kazis</div><div>I. Mylonas</div><div>P. Stathis</div><div>D. Vogiatzoglou</div><div>S.R. Bornstein</div><div>S. Honigman</div><div>B. Gross</div><div>Y. Lampl</div><div>J. Streifler</div><div>A. Capurso</div><div>G. Comi</div><div>N. Canal</div><div>L. Frattola</div><div>L.C. Gandolfo</div><div>M. Poloni</div><div>A. Mamoli</div><div>U. Senin</div><div>R. Rangel Guerra</div><div>J. de Keyser</div><div>A.M. Boon</div><div>J.A. Haas</div><div>D.J. Kamphuis</div><div>P.L.M. de Kort</div><div>P.J. Koudstaal</div><div>N.E. Anderson</div><div>R. Scott</div><div>G.P.J. Singh</div>
Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular diseasehttp://repub.eur.nl/pub/22493/
Tue, 01 Jul 2003 00:00:01 GMT<div>E.J. Topol</div><div>D. Easton</div><div>R.A. Harrington</div><div>P. Amarenco</div><div>R.M. Califf</div><div>C. Graffagnino</div><div>S.M. Davis</div><div>H.C. Diener</div><div>J.J. Ferguson</div><div>D. Fitzgerald</div><div>J.R. Granett</div><div>A. Shuaib</div><div>P.J. Koudstaal</div><div>P. Theroux</div><div>F.J.J. van de Werf</div><div>K.N. Sigmon</div><div>K.S. Pieper</div><div>M. Vallee</div><div>J.T. Willerson</div>
BACKGROUND: This is the primary report of the large-scale evaluation of lotrafiban, an orally administered IIb/IIIa receptor antagonist, a unique trial with respect to the platelet antagonist, protocol design, and inclusion of cerebrovascular disease in a significant proportion of patients.
METHODS AND RESULTS: Patients with vascular disease were randomized to lotrafiban 30 or 50 mg BID on the basis of age and predicted creatinine clearance or placebo in addition to aspirin at a dose ranging from 75 to 325 mg/d at the discretion of the physician-investigator. Follow-up was for up to 2 years. The primary end point was the composite of all-cause mortality, myocardial infarction, stroke, recurrent ischemia requiring hospitalization, and urgent revascularization. Of 9190 patients enrolled from 23 countries and 690 hospitals, 41% had cerebrovascular disease at the time of entry, and 59% had coronary artery disease. Death occurred in 2.3% of placebo-assigned patients and 3.0% of lotrafiban-group patients (hazard ratio 1.33, 95% CI 1.03 to 1.72, P=0.026), and the cause of excess death was vascular related. There was no significant difference in the primary end point (17.5% compared with 16.4%, respectively; hazard ratio 0.94, 95% CI 0.85 to 1.03, P=0.19). Serious bleeding was more frequent in the lotrafiban group (8.0% compared with 2.8%; P<0.001). Serious bleeding was more common among patients who received higher doses of aspirin (>162 mg/d), with or without lotrafiban.
CONCLUSIONS: Lotrafiban, an orally administered platelet glycoprotein IIb/IIIa blocker, induced a 33% increase in death rate, which was vascular in origin and not affected by the type of atherosclerotic involvement at entry to the trial. Although the dose of aspirin was not randomly assigned, the finding of increased bleeding with doses >162 mg/d is noteworthy.Lubeluzole in acute ischemic stroke treatment: A double-blind study with an 8-hour inclusion window comparing a 10-mg daily dose of lubeluzole with placebohttp://repub.eur.nl/pub/22507/
Wed, 01 Nov 2000 00:00:01 GMT<div>H.C. Diener</div><div>M. Cortens</div><div>G.A. Ford</div><div>J.C. Grotta</div><div>W. Hacke</div><div>M. Kaste</div><div>P.J. Koudstaal</div><div>T. Wessel</div>
BACKGROUND AND PURPOSE: This trial was a double-blind, placebo-controlled, phase III trial with an 8-hour inclusion window to assess the efficacy and safety of an intravenous loading dose of 7.5 mg followed by a daily intravenous dose of 10 mg lubeluzole for 5 days in acute ischemic stroke patients.
METHODS: A total of 1786 patients were randomized: 901 to lubeluzole and 885 to placebo. Overall, 212 patients (23.5%) from the lubeluzole group and 213 (24.1%) from the placebo group discontinued the trial prematurely. In the lubeluzole group 201 patients (22.3%) discontinued because of adverse events compared with 193 patients (21.8%) in the placebo group.
RESULTS: The primary population for the efficacy analysis comprised the core stroke patients (exclusion of older patients aged >75 years with severe stroke) in the 0- to 6-hour inclusion time window. The primary efficacy parameter was a 3-category functional status (Barthel Index 70 to 100/0 to 70/vegetative, dead) at week 12. In the lubeluzole group 207 patients (47.8%) were classified as mildly dependent/independent at week 12, 131 (30.3%) were moderately/severely dependent, and 95 (21.9%) were vegetative/dead. In the placebo group these numbers were 221 (54.4%), 112 (27.6%), and 73 (18.0%), respectively. Logistic regression analysis showed no statistically significant difference between the treatment groups (P:=0.162). Additionally, for none of the secondary efficacy parameters (mortality at week 12, modified Rankin score, total Barthel score) was a statistically significant difference between the lubeluzole and placebo groups obtained. There were no statistically significant differences between the 2 treatments for all treated patients, patients included within the 6- to 8-hour window, and patients with severe strokes aged >75 years. Overall, of all treated patients, 401 (22.5%) died: 203 (22.5%) in the lubeluzole group and 198 (22.4%) with placebo. Of all subjects treated, 853 (95%) on lubeluzole and 826 (93%) on placebo reported an adverse event during their treatment period or within the next 2 days after discontinuation of treatment. The most frequently observed adverse events were fever (25.9% lubeluzole; 23.4% placebo), constipation (20.2%; 19.7%), and headache (17.6%; 21.2%). Imbalances were found for atrial fibrillation (1.8% lubeluzole; 1.1% placebo) and QT prolongation (0.9%; 0.2%).
CONCLUSIONS: This study failed to show an efficacy of lubeluzole in the treatment of acute stroke. On the other hand, lubeluzole treatment by the current dosage schedule was not associated with a significant safety problem.Design of the blockade of the glycoprotein IIb/IIIa receptor to avoid vascular occlusion (BRAVO) trialhttp://repub.eur.nl/pub/55828/
Thu, 01 Jun 2000 00:00:01 GMT<div>E.J. Topol</div><div>J. Donald Easton</div><div>P. Amarenco</div><div>R.M. Califf</div><div>R.A. Harrington</div><div>C. Graffagnino</div><div>S.M. Davis</div><div>H.C. Diener</div><div>J.J. Ferguson</div><div>D. Fitzgerald</div><div>A. Shuaib</div><div>P.J. Koudstaal</div><div>P. Theroux</div><div>F.J.J. van de Werf</div><div>J.T. Willerson</div><div>R. Chan</div><div>J. Samuels</div><div>D.H. Ilson</div><div>J.R. Granett</div>
Familial hemiplegic migraine locus on 19p13 is involved in the common forms of migraine with and without aurahttp://repub.eur.nl/pub/55634/
Wed, 01 Nov 1995 00:00:01 GMT<div>A. May</div><div>R.A. Ophoff</div><div>G.M. Terwindt</div><div>C. Urban</div><div>R. van Eijk</div><div>J. Haan</div><div>H.C. Diener</div><div>D. Lindhout</div><div>R.R. Frants</div><div>L.A. Sandkuijl</div><div>M.D. Ferrari</div>
Migraine is a common neurological disease of two main types: migraine with aura and migraine without aura. Familial clustering suggests that genetic factors are involved in the etiology of migraine. Recently, a gene for familial hemiplegic migraine, a rare autosomal dominant subtype of migraine with aura, was mapped to chromosome 19p13. We tested the involvement of this chromosomal region in 28 unrelated families with the common forms of migraine with and without aura, by following the transmission of the highly informative marker D19S394. Sibpair analysis showed that affected sibs shared the same marker allele more frequently than expected by chance. Our findings thus also suggest the involvement of a gene on 19p13 in the etiology of the common forms of migraine.